Researchers have found that the vitamin D receptor promotes the differentiation of oligodendrocyte progenitor cells and enhances myelin sheath regeneration. The findings could lead to new remyelination enhancing drugs for multiple sclerosis patients and those suffering from other demyelinating diseases.
Multiple sclerosis patients experience continuous loss of the myelin that insulates neurons in the central nervous system. Oligodendrocyte progenitor cells (OPCs) migrate towards neurons and differentiate into myelin producing oligodendrocytes in response to demyelination, however this process slows as a person ages.
Retinoid X receptor gamma (RXR-ɣ) is a nuclear receptor protein that is known to promote OPC differentiation and remyelination. Nuclear receptors usually function in pairs; as such researchers led by Robin Franklin at the University of Cambridge (UK) investigated the role of RXR-ɣ and its binding partners in the process of remyelination.
The researchers found that RXR-ɣ bound to nuclear receptors, including the vitamin D receptor (VDR), in OPCs and oligodendrocytes. The findings also indicated that VDR inhibition leads to impaired OPC differentiation and reduced the cells’ capacity to remyelinate axons ex vivo. In contrast, the team found that Vitamin D increased OPC differentiation.
An association has previously been found between reduced vitamin D levels and the onset of multiple sclerosis. The new research suggests that vitamin D may also affect disease progression by controlling myelin sheath regeneration. It is hoped that VDR-activating drugs could promote remyelination in a range of demyelinating diseases.
The team are now looking to identify genes that are downstream targets of the RXR-γ–VDR heterodimer and whether other nuclear receptors paired with RXR-ɣ could also be involved in OPC differentiation and remyelination.